| 2013 |
Y26 phosphorylation of PGAM1 enhances its activation by releasing inhibitory E19 that blocks the active site, stabilizing cofactor 2,3-bisphosphoglycerate binding and H11 phosphorylation. Crystal structure of H11-phosphorylated PGAM1 revealed that phospho-H11 activates PGAM1 at least in part by promoting substrate 3-phosphoglycerate binding. |
Crystal structure determination, active-site mutagenesis, in vitro enzymatic assay |
Nature communications |
High |
23653202
|
| 2024 |
PKM2 moonlights as a histidine kinase to phosphorylate PGAM1 at H11 in a phosphoenolpyruvate (PEP)-dependent manner, activating PGAM1. Monomeric and dimeric (but not tetrameric) PKM2 are efficient for this phosphorylation. Src-catalyzed PGAM1 Y119 phosphorylation (induced by EGF signaling) is a prerequisite for PKM2 binding and subsequent H11 phosphorylation. Disruption of Y119 phosphorylation (via peptide or mutation) blocks the PGAM1-PKM2 interaction and dampens glycolysis shunts and tumor growth. |
In vitro kinase assay, Co-IP, mutagenesis (Y119 mutation), cell-permeable peptide disruption, mass spectrometry |
The EMBO journal |
High |
38750259
|
| 2022 |
Aspirin reduces PGAM1 succinylation at K99, suppressing PGAM1 enzymatic activity and glycolysis in hepatoma cells. Mechanistically, NF-κB p65 upregulates HAT1 (the succinylation writer for PGAM1), and aspirin reduces HAT1 expression via NF-κB. The PGAM1-K99R mutant failed to rescue aspirin-induced inhibition of PGAM1 activity, glycolysis, and proliferation, confirming K99 succinylation is functionally required. |
Site-directed mutagenesis (K99R), western blotting for succinylation, enzymatic activity assay, RNA-seq, in vivo tumor model |
Acta pharmacologica Sinica |
High |
35835856
|
| 2024 |
KAT2A interacts with PGAM1 and promotes its succinylation at the K161 residue, enhancing PGAM1 enzymatic activity and glycolysis in hepatocellular carcinoma cells. Astragaloside IV downregulates KAT2A, reducing PGAM1 succinylation and glycolysis. |
Co-immunoprecipitation, immunofluorescence, site-specific succinylation assay, PGAM1 inhibition rescue experiment, xenograft model |
BMC cancer |
Medium |
38835015
|
| 2022 |
USP46 directly interacts with PGAM1 and enhances its protein stability by reducing PGAM1 ubiquitination, thereby stimulating glycolysis and promoting TNBC cell growth and metastasis. |
Co-IP, ubiquitination assay, overexpression/knockdown functional assays |
Cell biology international |
Medium |
36335636
|
| 2025 |
SEC61G stabilizes PGAM1 protein by competitively inhibiting the E3 ubiquitin ligase UBE3C, preventing proteasomal degradation of PGAM1 and thereby enhancing glycolysis to support brain metastatic colonization in NSCLC. |
Co-IP, ubiquitination assay, transcriptomics, pharmacological inhibition, in vivo brain metastasis model |
International journal of biological sciences |
Medium |
39990664
|
| 2025 |
UBE2S interacts with PGAM1 and OTUB2 to inhibit K48-linked deubiquitylation of PGAM1, increasing PGAM1 protein levels, promoting DNA repair and reducing apoptosis, thereby decreasing GBM cell sensitivity to temozolomide. |
Immunoprecipitation coupled with mass spectrometry, Co-IP, ubiquitination assay, in vivo GBM mouse model |
International journal of biological macromolecules |
Medium |
39904430
|
| 2025 |
SYVN1 (E3 ubiquitin ligase) mediates K48-linked polyubiquitination and proteasomal degradation of PGAM1. Dihydrotanshinone I (DHT) induces this SYVN1-mediated degradation, disrupting glycolytic flux and suppressing HCC tumor growth. |
Proteasomal degradation assay, ubiquitination assay, in vitro glycolytic enzyme activity measurements, orthotopic and subcutaneous xenograft models |
Phytotherapy research : PTR |
Medium |
40640077
|
| 2026 |
JOSD1 deubiquitinase, together with AARS1, regulates a ubiquitination-lactylation crosstalk at K251 of PGAM1, stabilizing PGAM1, enhancing its enzymatic activity, and promoting lactate accumulation that impairs CD8+ T cell function in HCC. |
Multi-omics analysis, Co-IP, ubiquitination assay, lactylation detection, cell line and animal model experiments |
Gut |
Medium |
42049490
|
| 2023 |
PGAM1 inhibition promotes hepatocellular carcinoma cell ferroptosis by downregulating Lipocalin (LCN2) via energy stress and ROS-dependent AKT inhibition, which also downregulates PD-L1. An allosteric PGAM1 inhibitor (KH3) synergizes with anti-PD-1 immunotherapy in HCC models. |
In vitro and in vivo functional experiments, allosteric inhibitor (KH3), PDX models, subcutaneous and orthotopic HCC models |
Advanced science (Weinheim, Baden-Wurttemberg, Germany) |
Medium |
37705495
|
| 2019 |
An allosteric PGAM1 inhibitor (KH3), developed by structure-guided optimization, significantly suppresses PDAC cell proliferation by downregulating glycolysis and mitochondrial respiration in correlation with PGAM1 expression, similar to genetic PGAM1 depletion. |
Structure-guided drug design, cell proliferation assay, metabolic flux analysis (glycolysis/mitochondrial respiration), PDX models |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
31662475
|
| 2018 |
The S1P/S1PR3 axis inhibits YAP phosphorylation and promotes nuclear translocation of YAP, contributing to formation of a YAP-c-MYC complex that enhances transcription of PGAM1. This was shown by Co-IP of YAP-c-MYC interaction and ChIP demonstrating binding of YAP and c-MYC to the PGAM1 promoter. |
Co-immunoprecipitation (YAP-c-MYC), chromatin immunoprecipitation (PGAM1 promoter), luciferase reporter assay, RNA sequencing, XF96 metabolic flux analyzer |
EBioMedicine |
Medium |
30587459
|
| 2021 |
PGAM1 overexpression in glioma prevents inactivation of the ATM signaling pathway by sequestering the phosphatase WIP1 in the cytoplasm, promoting DNA damage response and conferring radio- and chemoresistance. Genetic inhibition of PGAM1 sensitizes glioma cells to DNA damage. |
Genetic knockdown/overexpression, subcellular fractionation/localization of WIP1, DNA damage assays |
Molecular & cellular oncology |
Medium |
33860077
|
| 2020 |
T cell-specific deletion of Pgam1 in mice attenuates both CD8 and CD4 T cell-dependent immune responses. Glycolysis (via PGAM1) augments mTORC1 and TCR signaling, and glutamine acts as a metabolic hub by increasing intracellular glutamine levels required to augment glycolysis and mTORC1 activity in activated T cells. |
T cell-specific Pgam1 knockout mice, metabolomics (Soga lab), mTORC1 and TCR signaling assays, in vivo immune challenge models |
Communications biology |
High |
32709928
|
| 2018 |
PGAM1 promotes epithelial-mesenchymal transition (EMT) of PDAC cells by regulating the Wnt/β-catenin pathway and is itself modulated by the PI3K/Akt/mTOR pathway as a novel downstream target. PGAM1 also has a positive mutual regulation with HIF-1α. |
siRNA silencing, western blotting for pathway components, proliferation/migration/invasion assays in pancreatic cancer cell lines |
Oncology research |
Low |
29386088
|
| 2023 |
Exosomal PGAM1 from prostate cancer cells binds to γ-actin (ACTG1) in HUVECs, promoting podosome formation and neovascular sprouting. PGAM1 also promotes invadopodia formation in PCa cells. |
GST pulldown, Co-immunoprecipitation, gelatin degradation assay, in vivo lung metastasis model (tail vein injection) |
Cell death & disease |
Medium |
37542027
|
| 2020 |
PGAM1 knockdown in breast cancer cells upregulates ASS1 expression through the cAMP/AMPK/CEBPB axis, suppressing proliferation, invasion, migration, and EMT. PGAM1 negatively regulates ASS1 expression via this signaling pathway. |
RNA sequencing, siRNA knockdown, pathway inhibitor assays, in vivo tumor models, immunohistochemistry |
Molecular oncology |
Low |
35674458
|
| 2020 |
PGAM1 directly interacted with TGF-β (shown by Co-IP), and cardiac-specific PGAM1 knockout in mice protected against myocardial ischemia-reperfusion injury by abrogating NF-κB, p38, JNK, and TGF-β signaling pathways, reducing inflammation, apoptosis, and fibrosis. |
Co-immunoprecipitation (PGAM1-TGF-β), cardiac-specific knockout mouse model, OGDR in vitro model, echocardiography, histology |
Biochemical and biophysical research communications |
Medium |
33168191
|
| 2018 |
NUDT7 knockdown upregulates PGAM1 expression, and overexpression of PGAM1 in chondrocytes induces lipid accumulation, IL-1β upregulation, and apoptotic cell death. These negative effects of PGAM1 on cartilage homeostasis are reversed by co-introduction of NUDT7, placing PGAM1 downstream of NUDT7 in OA pathogenesis. |
NUDT7 knockout mice, genome-wide analysis, PGAM1 overexpression in chondrocytes, co-rescue experiment |
Nature communications |
Medium |
30143643
|
| 2025 |
AUF1 (RNA-binding protein) promotes the decay of PGAM1 mRNA, suppressing glycolysis and cellular senescence. MST1 kinase phosphorylates AUF1, inactivating it and leading to PGAM1 mRNA stabilization and increased PGAM1 expression, accelerating senescence. |
mRNA decay assays, AUF1 overexpression/knockdown, MST1 kinase assay, RIP (RNA immunoprecipitation), proteomics profiling in human diploid fibroblasts |
Aging |
Medium |
40711448
|
| 2025 |
METTL5 directly targets PGAM1 mRNA through m6A modification, and YTHDF1 (an m6A reader) recognizes and binds methylated PGAM1 mRNA, enhancing its stability and expression, thereby promoting glycolysis in NSCLC. |
m6A methylation assay, RNA stability assay, western blotting, metabolic flux measurement (Seahorse), rescue experiment with PGAM1 overexpression in METTL5 knockdown cells |
Oncology letters |
Low |
42057886
|
| 2025 |
NAT10-mediated ac4C modification of PGAM1 mRNA enhances its stability, increasing PGAM1 expression and promoting glycolysis and cell stemness in ovarian cancer. NAT10 silencing reduced ac4C levels on PGAM1 mRNA and inhibited glycolysis; re-expression of PGAM1 reversed these effects. |
RNA immunoprecipitation (RIP), ac4C-specific RIP, RNA stability assay, sphere formation assay, dual-luciferase reporter, in vivo tumor growth |
Scientific reports |
Medium |
41198892
|
| 2026 |
PGAM1 promotes pathological oligomerization of VDAC1; this PGAM1-VDAC1 interaction (shown by Co-IP) triggers collapse of mitochondrial quality control and ER stress, leading to cytosolic leakage of mitochondrial DNA that activates the cGAS-STING pathway, ultimately causing cardiomyocyte ferroptosis in doxorubicin cardiotoxicity. |
Co-immunoprecipitation (PGAM1-VDAC1), cardiomyocyte-specific PGAM1 knockout mice, pharmacological VDAC1 oligomerization induction/inhibition, echocardiography, immunofluorescence, western blotting |
Free radical biology & medicine |
Medium |
41651300
|
| 2015 |
PGAM1 knockdown in bladder cancer cells upregulates its substrate 3-PG and downregulates its product 2-PG, demonstrating its enzymatic role in the glycolytic step from 3-PG to 2-PG, and consequently inhibits aerobic glycolysis and the oxidative pentose phosphate pathway essential for cancer cell proliferation. |
RNAi knockdown, metabolite measurement (3-PG, 2-PG), in vivo xenograft model |
Journal of proteomics |
Medium |
26655504
|
| 2023 |
RFX6 transcription factor binds to the promoter region of PGAM1 and upregulates its expression (ChIP confirmed), leading to enhanced glycolysis and HCC cell growth and metastasis. |
Chromatin immunoprecipitation (RFX6 on PGAM1 promoter), untargeted metabolome profiling, functional assays in vitro and in vivo |
Clinical and translational medicine |
Medium |
38093528
|
| 2026 |
PGAM1 knockdown induces G2/M cell cycle arrest in TNBC cells and impairs glycolytic flux by reducing rate-limiting enzyme activities and pyruvate entry into the TCA cycle. Reduced lactate secretion following PGAM1 knockdown inhibits M2-type tumor-associated macrophage polarization in co-culture systems. |
siRNA knockdown, cell cycle analysis, glycolytic enzyme activity assay, metabolic flux measurement, macrophage co-culture system |
IUBMB life |
Medium |
42204131
|
| 1982 |
The PGAM1 (PGAMA) gene was assigned to human chromosome 10q26.1 (or 10q25.3) by gene dosage studies in patients with chromosomal trisomy or monosomy for that region. |
Gene dosage studies in erythrocytes from chromosomally abnormal patients |
Annales de genetique |
Medium |
6282177
|